biostudies-literatureUnknown43(8)Wang JCMacrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 μM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with Acta pharmacologica Sinica2016-2025https://www.ebi.ac.uk/biostudies/studies/S-EPMC9343373biostudies-literatureSapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages.PMC9343373Zhang LLLou DYZhou QWang JCShi QWeng QJHe QJYang BZhou LQWang JJQiu YPfalseSapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages.Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 μM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with 2022-01-01T00:00:00Z2022 Aug2025-04-05T11:47:54.843Z2025-04-05T11:47:54.843ZS-EPMC93433733502254210.1038/s41401-021-00842-x